Recent epidemiologic evidence has suggested a link between persistent gastric infection with H. pylori in human patients and the development of gastric carcinoma, but a direct causal relationship has not been established, and the mechanism by which bacterial infection leads to malignant transformation is not known. The suggestion that primary bacterial infection can lead to carcinogenesis is an important one, however, and new approaches to test this hypothesis are necessary. The primary goal of this proposal is use an animal model to determine if there is a direct causal link between gastric helicobacter infection and gastric carcinogenesis. The overall hypothesis addressed is that chronic persistent helicobacter gastritis leads to premalignant changes and that contact with a primary carcinogen (mutagen) leads to eventual malignant transformation of gastric epithelial cells. The proposed mechanism for such transformation is the secretion of specific inflammatory mediators which lead to non-neoplastic epithelial proliferation. This proliferation allows fixation of mutations induced by a primary carcinogen. An established model of helicobacter gastritis in mice will be used to determine if chemically-induced carcinogenesis is dependent upon helicobacter-associated gastritis, and to test the hypothesis that malignant transformation is dependent on release of T cell mediators leading to epithelial hyperplasia and dysplasia.